Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
Neurological Sciences
Published in: Neurological Sciences 9/2023

17-04-2023 | Constipation | Original Article

Parkinson’s disease patients combined with constipation tend to have higher serum expression of microRNA 29c, prominent neuropsychiatric disorders, possible RBD conversion, and a substandard quality of life

Authors: Hong Liu, Lei Shen, Haonan Zhao, Jie Yang, Dongya Huang

Published in: Neurological Sciences | Issue 9/2023

Login to get access

Abstract

Introduction

The symptom of constipation has been confirmed as an early diagnose criteria for Parkinson’s disease (PD). Furthermore, evidences suggest that pathogenesis of PD initiates in gut, rather than brain. If so, identifying biomarkers for constipation in PD might have potentials to assist early diagnosis and initial treatment.

Method

We first identified that microRNA 29c (miR-29c) was dysregulated both in PD and constipation patients through bioinformatics analysis. Then, serological analysis of the expression of miR-29c in 67 PD patients with constipation (PD–C), 51 PD patients without constipation (PD-NC), and 50 healthy controls (HC) was carried out by qPCR. Demographic and clinical features were also compared. Patients in PD–C group were further classified into two groups: those with prodromal stage constipation (PD–C-Pro) (n = 36) and those with clinical stage constipation (PD–C-Clinic) (n = 31), to explore their different characteristics.

Results

The levels of miR-29c in PD–C group were higher than that in PD-NC group, both higher than HC group. PD–C-Pro group’s miR-29c levels were statistically higher compared with PD–C-Clinic group’s. What is more, PD–C group had higher scores of MDS-UPDRS-I, NMSS, NMSS3, NMSS4, NMSS6, NMSS9, SCOPA-AUT, HAMD, HAMA, RBDSQ, CSS, and PACQOL compared with PD-NC party. Relative to the PD–C-Clinic, patients in PD–C-Pro group had higher MDS-UPDRS-I, NMSS, NMSS3, HAMD, and HAMA scores, and were more likely to have RBD.

Conclusion

Our results indicated that miR-29c seems to be an underlying cause for developing constipation in patients with PD and PD–C identifies a group of patients with more severe non-motor impairment, prominent neuropsychiatric disorders, and possible RBD conversion as well as a substandard quality of life. We further confirmed that there is a close relationship between symptoms representing the same pathological origin, especially constipation and RBD.
Literature
1.
Makaroff L, Gunn A, Gervasoni C et al (2011) Gastrointestinal disorders in Parkinson’s disease: prevalence and health outcomes in a US claims database. J Parkinsons Dis 1(1):65–74PubMedCrossRef
2.
Chen Z, Li G, Liu J (2020) Autonomic dysfunction in Parkinson’s disease: implications for pathophysiology, diagnosis, and treatment. Neurobiol Dis 134:104700PubMedCrossRef
3.
Adams-Carr KL, Bestwick JP, Shribman S et al (2016) Constipation preceding Parkinson’s disease: a systematic review and meta-analysis. J Neurol Neurosurg J Pre-proof Psychiatry 87(7):710–716CrossRef
4.
5.
Long JM, Lahiri DK (2011) Current drug targets for modulating Alzheimer’s amyloid precursor protein: role of specific micro-RNA species. Curr Med Chem 18(22):3314–3321PubMedCrossRef
6.
Wang R, Chopra N, Nho K et al (2022) Human microRNA (miR-20b-5p) modulates Alzheimer’s disease pathways and neuronal function, and a specific polymorphism close to the miR20b gene influences Alzheimer’s biomarkers. Mol Psychiatry 27(2):1256–1273PubMedPubMedCentralCrossRef
7.
Soto M, Iranzo A, Lahoz S et al (2022) Serum MicroRNAs predict isolated rapid eye movement sleep behavior disorder and Lewy body diseases. Mov Disord 37(10):2086–2098PubMedPubMedCentralCrossRef
8.
9.
Ma W, Li Y, Wang C et al (2016) Serum miR-221 serves as a biomarker for Parkinson’s disease. Cell Biochem Funct 34(7):511–515PubMedCrossRef
10.
Ozdilek B, Demircan B (2021) Serum microRNA expression levels in Turkish patients with Parkinson’s disease. Int J Neurosci 131(12):1181–1189PubMedCrossRef
11.
Ardashirova NS, Abramycheva NY, Fedotova EY et al (2022) MicroRNA expression profile changes in the leukocytes of Parkinson’s disease patients. Acta Naturae 14(3):79–84PubMedPubMedCentralCrossRef
12.
Jiang Y, Chen J, Sun Y et al (2021) Profiling of differentially expressed MicroRNAs in saliva of Parkinson’s disease patients. Front Neurol 12:738530PubMedPubMedCentralCrossRef
13.
Botta-Orfila T, Morató X, Compta Y et al (2014) Identification of blood serum micro-RNAs associated with idiopathic and LRRK2 Parkinson’s disease. J Neurosci Res 92(8):1071–1077PubMedCrossRef
14.
Shen L, Zhou K, Liu H et al (2022) Prediction of mechanosensitive genes in vascular endothelial cells under high wall shear stress. Front Genet 12:796812PubMedPubMedCentralCrossRef
15.
16.
Huang AC, Jiang T, Liu YX et al (2019) A specialized metabolic network selectively modulates Arabidopsis root microbiota. Science 364(6440):eaau6389PubMedCrossRef
17.
Venn J (1880) On the diagrammatic and mechanical representation of propositions and reasonings. Phil Mag 9(59):1–18CrossRef
18.
19.
20.
Palsson OS, Whitehead WE, van Tilburg MA et al (2016) Rome IV diagnostic questionnaires and tables for investigators and clinicians. Gastroenterology S0016–5085(16):00180–00183
21.
22.
Goetz CG, Tilley BC, Shaftman SR et al (2008) Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS): scale presentation and clinimetric testing results. Mov Disord 23(15):2129–2170PubMedCrossRef
23.
Chaudhuri KR, Martinez-Martin P, Schapira AH et al (2006) International multicenter pilot study of the first comprehensive self-completed nonmotor symptoms questionnaire for Parkinson’s disease: the NMSQuest study. Mov Disord 21(7):916–923PubMedCrossRef
24.
Visser M, Marinus J, Stiggelbout AM et al (2004) Assessment of autonomic dysfunction in Parkinson’s disease: the SCOPA-AUT. Mov Disord 19(11):1306–1312PubMedCrossRef
25.
Folstein MF, Folstein SE, McHugh PR (1975) “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3):189–198PubMedCrossRef
26.
Chaudhuri KR, Pal S, DiMarco A et al (2002) The Parkinson’s disease sleep scale: a new instrument for assessing sleep and nocturnal disability in Parkinson’s disease. J Neurol Neurosurg Psychiatry 73(6):629–635PubMedPubMedCentralCrossRef
27.
Johns MW (1991) A new method for measuring daytime sleepiness: the Epworth sleepiness scale. Sleep 14(6):540e5CrossRef
28.
Walters AS, LeBrocq C, Dhar A et al (2003) Validation of the International Restless Legs Syndrome Study Group rating scale for restless legs syndrome. Sleep Med 4(2):121–132PubMedCrossRef
29.
Wang Y, Wang ZW, Yang YC et al (2015) Validation of the rapid eye movement sleep behavior disorder screening questionnaire in China. J Clin Neurosci 22(9):1420–1424PubMedCrossRef
30.
31.
32.
Peto V, Jenkinson C, Fitzpatrick R et al (1995) The development and validation of a short measure of functioning and well being for individuals with Parkinson’s disease. Qual Life Res 4(3):241–248PubMedCrossRef
33.
Mlinac ME, Feng MC (2016) Assessment of activities of daily living, self-care, and independence. Arch Clin Neuropsychol 31(6):506–516PubMedCrossRef
34.
Cressatti M, Juwara L, Galindez JM et al (2020) Salivary microR-153 and microR-223 levels as potential diagnostic biomarkers of idiopathic Parkinson’s disease. Mov Disord 35(3):468–477PubMedCrossRef
35.
Marquis P, De La Loge C, Dubois D et al (2005) Development and validation of the patient assessment of constipation quality of life questionnaire. Scand J Gastroenterol 40(5):540–551PubMedCrossRef
36.
Agachan F, Chen T, Pfeifer J et al (1996) A constipation scoring system to simplify evaluation and management of constipated patients. Dis Colon Rectum 39(6):681–685PubMedCrossRef
37.
38.
Knudsen K, Krogh K, Østergaard K et al (2017) Constipation in parkinson’s disease: subjective symptoms, objective markers, and new perspectives. Mov Disord 32(1):94–105PubMedCrossRef
39.
Gan J, Wan Y, Shi J et al (2018) A survey of subjective constipation in Parkinson’s disease patients in Shanghai and literature review. BMC Neurol 18(1):29PubMedPubMedCentralCrossRef
40.
Vriesman MH, Koppen IJN, Camilleri M et al (2020) Management of functional constipation in children and adults. Nat Rev Gastroenterol Hepatol 17(1):21–39PubMedCrossRef
41.
42.
Wu F, Zikusoka M, Trindale A et al (2008) MicroRNAs are differentially expressed in ulcerative colitis and alter expression of macrophage inflammatory peptide-2 alpha. Gastroenterology 135:1624–1635PubMedCrossRef
43.
Zhou Q, Costinean S, Croce CM et al (2015) MicroRNA 29 targets nuclear factor-kappaB-repressing factor and Claudin 1 to increase intestinal permeability. Gastroenterology 148:158-169.e8PubMedCrossRef
44.
Zhou Q, Souba WW, Croce C et al (2010) MicroRNA-29a regulates intestinal membrane permeability in patients with irritable bowel syndrome. Gut 59:775–784PubMedCrossRef
45.
Leta V, Urso D, Batzu L et al (2021) Constipation is associated with development of cognitive impairment in de novo Parkinson’s disease: a longitudinal analysis of two international cohorts. J Parkinsons Dis 11(3):1209–1219PubMedCrossRef
46.
Pagano G, Yousaf T, Wilson H et al (2018) Constipation is not associated with dopamine transporter pathology in early drug-naïve patients with Parkinson’s disease. Eur J Neurol 25(2):307–312PubMedCrossRef
47.
Neikrug AB, Avanzino JA, Liu L et al (2014) Parkinson’s disease and REM sleep behavior disorder result in increased non-motor symptoms. Sleep Med 15:959–966PubMedPubMedCentralCrossRef
48.
Fereshtehnejad SM, Romenets SR, Anang JB et al (2015) New clinical subtypes of Parkinson disease and their longitudinal progression: a prospective cohort comparison with other phenotypes. JAMA Neurol 72:863–873PubMedCrossRef
49.
Kashihara K, Imamura T, Shinya T (2010) Cardiac 123I-MIBG uptake is reduced more markedly in patients with REM sleep behavior disorder than in those with early stage Parkinson’s disease. Parkinsonism Relat Disord 16:252–255PubMedCrossRef
50.
Horsager J, Andersen KB, Knudsen K et al (2020) Brain-first versus body-first Parkinson’s disease: a multimodal imaging case-control study. Brain 143(10):3077–3088PubMedCrossRef
51.
Fearon C, Lang AE, Espay AJ (2021) The logic and pitfalls of Parkinson’s disease as “brain-first” versus “body-first” subtypes. Mov Disord 36(3):594–598PubMedCrossRef
52.
Gjerstad MD, Boeve B, Wentzel-Larsen T et al (2008) Occurrence and clinical correlates of REM sleep behaviour disorder in patients with Parkinson’s disease over time. J Neurol Neurosurg Psychiatry 79(4):387–391PubMedCrossRef
53.
Hepp DH, Ruiter AM, Galis Y et al (2013) Pedunculopontine cholinergic cell loss in hallucinating Parkinson disease patients but not in dementia with Lewy bodies patients. J Neuropathol Exp Neurol 72(12):1162–1170CrossRef
54.
Geddes MR, Tie Y, Gabrieli JD et al (2016) Altered functional connectivity in lesional peduncular hallucinosis with REM sleep behavior disorder. Cortex 74:96–106PubMedCrossRef
55.
56.
Sun BH, Wang T, Li NY et al (2021) Clinical features and relative factors of constipation in a cohort of Chinese patients with Parkinson’s disease. World J Gastrointest Pharmacol Ther 12(1):21–31PubMedPubMedCentralCrossRef
57.
58.
Svensson E, Horváth-Puhó E, Thomsen RW et al (2015) Vagotomy and subsequent risk of Parkinson’s disease. Ann Neurol 78(4):522–529PubMedCrossRef
59.
Camacho M, Macleod AD, Maple-Grødem J et al (2021) Early constipation predicts faster dementia onset in Parkinson’s disease. NPJ Parkinsons Dis 7(1):45PubMedPubMedCentralCrossRef
60.
Bansal NR, Paul BS, Paul G et al (2022) Gender differences and impact of autonomic disturbance on fatigue and quality of life in Parkinson’s disease. Neurol India 70(1):203–208PubMed
61.
Song W, Guo X, Chen K et al (2014) The impact of non-motor symptoms on the Health-Related Quality of Life of Parkinson’s disease patients from Southwest China. Parkinsonism Relat Disord 20(2):149–152PubMedCrossRef
62.
Pilipovich AA, Vorob’eva OV, Makarov SA et al (2022) Gastrointestinal dysfunction impact on life quality in a cohort of Russian patients with Parkinson’s disease I-III H&Y stage. Parkinsons Dis 2022:1571801PubMedPubMedCentral
63.
Sakakibara R, Ogata T, Aiba Y et al (2020) Does depression contribute to the bladder and bowel complaint in Parkinson’s disease patients? Mov Disord Clin Pract 8(2):240–244PubMedPubMedCentralCrossRef
64.
Garvey M, Noyes R Jr, Yates W (1990) Frequency of constipation in major depression: relationship to other clinical variables. Psychosomatics 31(2):204–206PubMedCrossRef
Metadata
Title
Parkinson’s disease patients combined with constipation tend to have higher serum expression of microRNA 29c, prominent neuropsychiatric disorders, possible RBD conversion, and a substandard quality of life
Authors
Hong Liu
Lei Shen
Haonan Zhao
Jie Yang
Dongya Huang
Publication date
17-04-2023
Publisher
Springer International Publishing
Published in
Neurological Sciences / Issue 9/2023
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-023-06793-x

Other articles of this Issue 9/2023

Neurological Sciences 9/2023 Go to the issue

Letter to the Editor

Myasthenia gravis-myositis association: is it an overlap myositis or a distinct entity?

Brief Communication

Influence of kidney function and CSF/serum albumin ratio on plasma Aβ42 and Aβ40 levels measured on a fully automated platform in patients with Alzheimer’s disease

Original Article

Behavioral scales variability in patients with prolonged disorders of consciousness

Editorial

Cochrane neurological sciences field corner

Original Article

Shaping the course of early-onset Parkinson’s disease: insights from a longitudinal cohort

Original Article

Exploring depression in Parkinson’s disease: an Italian Delphi Consensus on phenomenology, diagnosis, and management